Known processes for producing R(-)-mandelic acid from chemically synthesized R,S-mandelic acid (i.e., a racemate) include (1) racemic resolution by fractional crystallization (see JP-A-58-177933, the term "JP-A" as used herein means an "unexamined published Japanese patent application"), (2) racemic resolution by chromatography (see, European Patent Publication No. 98 707A), (3) racemic resolution of a racemate ester by enzymatic asymmetric hydrolysis (see, K. Mori, et al., Tetrahedron, Vol. 36, p. 91 (1980)), and (4) chemical asymmetric synthesis by using a chiral reagent (see, D.A. Evans, et al., J. Am. Chem. Soc., Vol. 107, p. 4346 (1985)).
Known biological processes for producing R(-)-mandelic acid include, in addition to the above-described asymmetric hydrolysis of a racemic ester, (5) microbial asymmetric reduction of benzoylformic acid (see JP-A-57-198096). Further, known biological processes for producing R(-)-mandelic acid and its derivatives include (6) hydrolysis of R(-)-mandelonitrile or a substituted R(-)-mandelonitrile which is obtained by asymmetric synthesis using D-oxynitrilase (see JP-A-63-219388 and JP-A-2-5885) and (7) asymmetric hydrolysis of mandelonitrile or a substituted mandelonitrile or mandelamide or a substituted mandelamide by the action of a microorganism belonging to the genus Alcaligenes, Pseudomonas, Rhodopsuedomonas, Corynebacterium, Acinetobacter, Bacillus, Mycobacterium, Rhodococcus, or Candida (see, JP-A-84198 corresponding to European Patent Publication No. 0 348 901 A).
All of processes (1) to (3), consisting of racemic resolution, involve complicated steps which cause a reduction in yield for every step. Process (4), consisting of asymmetric synthesis, requires use of an expensive chiral reagent as a catalyst and does not yield products of high optical purity. Biological process (5), consisting of asymmetric reduction of benzoylformic acid, inherently contains difficulties in synthesizing a substrate and maintaining an NADH reconstitution system. The disclosure for process (6), called a D-oxynitrilase process, is no more than a statement that optically active mandelic acid or substituted mandelic acid has been obtained, additional follow-up studies are needed before industrialization would be possible. Process (7), consisting of asymmetric hydrolysis of mandelonitrile, a substituted mandelonitrile, mandelamide, or a substituted mandelamide does not produce one optically active compound directly from a racemate predominantly over the other optically active compound and hence involves handling both optically active compounds together. According to the disclosure of JP-A-2-84198 supra, the unreacted residual nitrile or amide having the undesired optical activity is recovered and converted to an organic acid having the opposite optical activity by acid hydrolysis or to a racemate by alkali treatment; this product is then used as a starting material for the production of R(-)-mandelic acid.
Such procedures for the separation of residual mandelonitrile or mandelamide, etc. of the other opposite activity and for racemization by alkali treatment make for a complicated process, which ultimately reduces the yield. Moreover, JP-A-2-84198 gives no specific example for production of an R(-)-mandelic acid derivative from a substituted mandelonitrile, leaving open the question as to whether an R(-)-mandelic acid derivative could be obtained with efficiency and high optical purity.
Thus, known processes are unsatisfactory for the industrial production of R(-)-mandelic acid and derivatives thereof.